Innovations in science have led to the development of laboratory-grown, three-dimensional tissues that mimic the properties of human skin. These platforms, known as skin models or skin equivalents, are constructed from human cells to replicate the skin’s structure and function. They provide researchers with a human-relevant tool to study skin biology, addressing challenges in dermatological research and product testing.
The Construction of Skin Models
The creation of a skin model is a meticulous process that begins with two primary components: human skin cells and a structural scaffold. The cells are keratinocytes, which form the skin’s outer protective layer, and fibroblasts, which produce the connective tissue of the dermis. These cells can be sourced from cell lines or from primary human tissue. The scaffold is a supportive matrix, often made from biological materials like collagen, that provides a structure for the cells to grow on, mimicking the skin’s extracellular matrix.
The laboratory procedure involves building the skin layer by layer. First, fibroblasts are seeded into the collagen gel to create a dermal equivalent. This mixture is cultured for several days in a nutrient-rich medium, allowing the fibroblasts to form a living dermal layer. Keratinocytes are then seeded on top of the newly formed dermal base.
The process then requires the introduction of an air-liquid interface. After an initial period of submerged growth, the culture medium is lowered so the top layer of keratinocytes is exposed to the air. This exposure triggers the keratinocytes to differentiate and stratify, forming the multiple distinct layers of a functional epidermis, including a protective outer barrier called the stratum corneum. This reconstruction process can take between 10 and 30 days.
Varieties of Reconstructed Skin
Skin models are designed with varying levels of complexity to suit different scientific needs. The most basic type is the Reconstructed Human Epidermis (RHE) model. Composed solely of keratinocytes grown on an inert filter or scaffold, RHE models replicate the epidermis, the skin’s outermost layer. Their structure is sufficient for foundational safety tests, such as assessing whether a chemical will cause skin irritation.
A more complex iteration is the full-thickness skin model, also known as a human skin equivalent (HSE). These models are more analogous to human skin because they include both a dermal layer with fibroblasts and an epidermal layer of keratinocytes. The presence of a living dermis allows for more complex studies, such as examining interactions between the dermal and epidermal layers or the efficacy of anti-aging compounds.
Beyond these standard models, researchers have developed specialized versions to investigate specific biological functions. Pigmented skin models, for example, incorporate melanocytes—the cells that produce melanin—into the epidermal layer. These are used to study pigmentation, the effects of UV radiation, and the safety of skin-lightening agents. More advanced models may include immune cells to study inflammatory responses and allergic reactions.
Applications in Research and Industry
A primary driver for the adoption of skin models has been the need for ethical alternatives to animal testing, particularly in the cosmetics industry where such testing is banned in many regions. These models are widely used for safety and efficacy assessments of consumer products. They are employed in validated tests to determine a substance’s potential for skin corrosion, irritation, and phototoxicity. Companies use these models to substantiate product claims, like measuring improvements in barrier function from a moisturizer.
In the pharmaceutical sector, skin models serve a range of functions. They are used to study the dermal absorption and penetration of topical drugs, helping scientists understand how much of an active ingredient reaches its target. These models are also used in wound healing research, allowing for the observation of tissue repair. Another use is screening new drug candidates for toxicity to identify potential irritants early in development.
Advanced skin models are also applied to the study of skin diseases. By using cells from patients or by manipulating culture conditions, scientists can create models that mimic diseases like psoriasis, atopic dermatitis (eczema), or skin cancer. These disease models provide an opportunity to investigate the underlying mechanisms of a condition and to test the efficacy of potential treatments on tissue that reflects the specific pathology.
Comparing Skin Models to Real Skin
Reconstructed skin models successfully replicate many features of human skin. Histologically, they show a well-stratified epidermis with distinct layers that closely resembles native skin. Functionally, they form a competent barrier that regulates water loss and prevents the penetration of harmful substances. This makes them reliable for many toxicological and dermatological applications.
Despite these successes, current skin models do not fully replicate the complexity of a living organ. A major difference is the absence of a vascular network, meaning they lack the blood vessels necessary for nutrient supply and for studying systemic absorption. Most models also lack skin appendages such as hair follicles, sebaceous glands, and sweat glands.
These lab-grown tissues are also not connected to a nervous system, so they cannot be used to study sensations like itching or pain. While some advanced models incorporate immune cells, they cannot reproduce the full, dynamic immune response. The models also have a limited lifespan, lasting only a few weeks, and do not undergo the long-term aging processes or chronic environmental exposures that human skin experiences.